The specific aim of this competitive renewal application is to extend data collection in our existing cohort of Caucasian and African American children, so that data on changes in body composition, abdominal fat distribution and insulin action and secretion are obtained in all children to the point of achieving full maturation. Progress: We have established a successful cohort study and made considerable progress towards understanding differences in metabolic risk factors that occur during early pubertal growth (to the point of mid-puberty), how these are influenced by body fat and visceral fat, and especially how these differ between African American and Caucasian children. We have shown that African American children have unfavorable differences in glucose metabolism (hyperinsulinemia, reduced insulin sensitivity, and increased acute insulin response) that remain highly significant even after adjusting for differences in body composition, fat distribution, physical activity and dietary factors. We have shown that the transition from Tanner Ito Ill is associated with a 33% reduction in insulin sensitivity with a lower than expected rise in the acute insulin response. This pubertal fall in insulin sensitivity is independent of obesity status and consistent across gender and ethnic groups. Based on these findings and other preliminary data we are proposing two new hypotheses. Hypothesis 1: Insulin sensitivity will increase and the acute insulin response will decrease from Tanner Ill to Tanner V towards the levels observed prior to puberty. However, the overall recovery of insulin sensitivity and the acute insulin response, as indicated by the change in the disposition index will be poorer in African American children and more obese children; Hypothesis 2:Glucose tolerance will be maintained during puberty by an increase in first-phase insulin secretion except in the most susceptible of individuals (e.g. African-American females) who will show an impairment in first-phase insulin secretion with progression of puberty. Summary: This competitive renewal provides a unique opportunity to examine the nature of transient insulin resistance during puberty, and especially how this may differ in African American children who are at increased risk for type 2 diabetes during puberty.
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